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Saint-Clément-de-la-Place, France

Barth H.,Hopitaux Universitaires Of Strasbourg
World Journal of Hepatology | Year: 2015

The majority of individuals exposed to hepatitis C virus (HCV) establish a persistent infection, which is a leading cause of chronic liver disease, cirrhosis and hepatocellular carcinoma. Major progress has been made during the past twenty-five years in understanding the HCV life cycle and immune responses against HCV infection. Increasing evidence indicates that host genetic factors can significantly influence the outcome of HCV infection and the response to interferon alpha-based antiviral therapy. The arrival of highly effective and convenient treatment regimens for patients chronically infected with HCV has improved prospects for the eradication of HCV worldwide. Clinical trials are evaluating the best anti-viral drug combination, treatment doses and duration. The new treatments are better-tolerated and have shown success rates of more than 95%. However, the recent breakthrough in HCV treatment raises new questions and challenges, including the identification of HCVinfected patients and to link them to appropriate health care, the high pricing of HCV drugs, the emergence of drug resistance or naturally occurring polymorphism in HCV sequences which can compromise HCV treatment response. Finally, we still do not have a vaccine against HCV. In this concise review, we will highlight the progress made in understanding HCV infection and therapy. We will focus on the most significant unsolved problems and the key future challenges in the management of HCV infection. © The Author(s) 2015. Published by Baishideng Publishing Group Inc. Source

Zeisel M.B.,University of Strasbourg | Lupberger J.,University of Strasbourg | Fofana I.,University of Strasbourg | Baumert T.F.,University of Strasbourg | Baumert T.F.,Hopitaux Universitaires Of Strasbourg
Journal of Hepatology | Year: 2013

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and hepatocellular carcinoma worldwide. Furthermore, HCV-induced liver disease is a major indication of liver transplantation. In the past years, direct-acting antivirals (DAAs) targeting HCV enzymes have been developed. DAAs increase the virologic response to anti-HCV therapy but may lead to selection of drug-resistant variants and treatment failure. To date, strategies to prevent HCV infection are still lacking and antiviral therapy in immunocompromised patients, patients with advanced liver disease and HIV/HCV-co-infection remains limited. Alternative or complementary approaches addressing the limitations of current antiviral therapies are to boost the host's innate immunity or interfere with host factors required for pathogenesis. Host-targeting agents (HTAs) provide an interesting perspective for novel antiviral strategies against viral hepatitis since they have (i) a high genetic barrier to resistance, (ii) a pan-genotypic antiviral activity, and (iii) complementary mechanisms of action to DAAs and might therefore act in a synergistic manner with current standard of care or DAAs in clinical development. This review highlights HTAs against HCV infection that have potential as novel antivirals and are in preclinical or clinical development. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Source

Andres E.,University of Strasbourg | Andres E.,Hopitaux Universitaires Of Strasbourg
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2012

Cationic host-defence antimicrobial peptides are recognised as an important component of the innate immune response in most multicellular organisms. In humans, several antimicrobial peptides have recently been recognised as key factors in the pathology of diseases such as cystic fibrosis, septic shock, atopic dermatitis and morbus Kostmann. To date, several hundred cationic antimicrobial peptides have been characterised. They are amphipathic peptides, comprising 20 to 50 amino acids, and exhibiting large structural diversity. These peptides display a broad spectrum of activity against bacterial, fungal and viral pathogens. Their mode of action is best known for cecropins and magainins, which act upon the cytoplasmic membrane of microorganisms, causing its disruption by a detergent-like activity and pore formation. In the last few years, several of these peptides or analogues (derived from magainin, protegrin, indolicidin and histatin) were in advanced clinical development, especially for localised infections (oral and cutaneous infections, pneumonias etc.). Several other molecules (rBPI, heliomicin and thanatin) are currently under development for various systemic infections (Staphylococcus sp., Aspergillus sp., Candida sp. etc.) and may represent important additions to the anti-infectious therapeutic arsenal. © Springer-Verlag 2011. Source

Cribier B.,Hopitaux Universitaires Of Strasbourg
Annales de Dermatologie et de Venereologie | Year: 2014

For a long time rosacea was thought to be mainly a vascular disorder. In the past ten years many other concepts have emerged, such as the neurovascular aspects and involvement of innate immunity. There is obviously a genetic part in rosacea, as it is much more common in people with fair skin, blue eyes and Celtic ascendance. The same persons are submitted to continental weather, with major temperature seasonal variations. Erythema and telangiectasia result from dilated superficial capillaries that have bizarre shapes, and induce constant edema of the dermis. This might be a favouring factor for Demodex colonization, which plays a major role in rosacea. Inflammation is always present, even in erythematotelangiectatic subtypes. It involves innate immunity, in response to environmental factors, like Demodex and its own biotope, resulting in overproduction of LL37, a pro-inflammatory peptide able to induce skin inflammation in an animal model, trough activation of inflammatory cells. Tool like receptors are involved in the activation of innate immunity. Demodex is the cause of ganulomas seen in papulopustular rosacea, but it is also always present in the erythematotelangiectatic subtypoe. Colonization by Demodex is nevertheless not decreased with conventional treatments of rosacea, like tetracyclins and metronizaole. This might be due to induction of inflamation by bacteria hosted by Demodex, like Bacillus oleronius, and dozens of bacteria that are being investigated. Finaly, rhinophyma is linked to both vascular changes and activation of fibrosis, involving TGF beta. © 2014 Elsevier Masson SAS. All rights reserved. Source

Durand E.,Hopitaux Universitaires Of Strasbourg
Seminars in Nuclear Medicine | Year: 2014

Nuclear medicine and MRI provide information about renal perfusion, function (glomerular filtration rate), and drainage. Some tracers that are used in nuclear medicine (technetium-diethylene triamine pentaacetic acid ([ 99mTc-DTPA] and 51chromium-EDTA) and some contrast media (CM) that are used for MRI (gadolinium-DTPA for instance) share the same pharmacokinetic properties, though, detection techniques are different (low-spatial resolution 2-dimensional projection with a good concentration-to-signal linearity for nuclear medicine and high-resolution 3-dimensional localization with nonlinear behavior for MRI). Thus, though based on the same principles, the methods are not the same and they provide somewhat different information. Many MRI perfusion studies have been conducted; some of them were compared with nuclear medicine with no good agreement. Phase contrast can reliably assess global renal blood flow but not perfusion at a tissular level. Arterial spin labeling has not proven to be a reliable tool to measure renal perfusion. Techniques using CM theoretically can assess perfusion at the tissular level, but they have not proven to be precise. To assess renal function, many models have been proposed. Some MRI techniques using CM, both semiquantitative (Patlak) and quantitative, have shown ability to roughly assess relative function. Some quantitative methods (Annet's and Lee's methods) have even showed that they could roughly estimate absolute renal function, with better results than estimated glomerular filtration rate. Quantification of drainage has not been much studied using MRI. © 2014 Elsevier Inc. Source

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